- Email: [email protected]
Infective Complications in Renal Allograft Recipients: Epidemiology and Outcome
COMPLICATIONS Infections
Infective Complications in Renal Allograft Recipients: Epidemiology and Outcome M. Veroux, G. Giuffrida, D. Corona, M. Gagliano, V. Scriffignano, D. Vizcarra, T. Tallarita, D. Zerbo, C. Virgilio, A. Sciacca, D. Cappello, S. Stefani, and P. Veroux ABSTRACT Introduction. Successful renal transplantation strictly depends on good control of rejection and better prevention and treatment of infections, which remain serious threats. Methods. This retrospective, observational study of 245 renal allograft recipients who underwent transplantation between January 2002 and December 2005 included a 21 ⫾ 10 months follow-up. Results. A total of 110 (44.9%) patients developed an infective process during the posttransplantation period, namely, 232 infective processes. Eighty patients developed at least 1 episode of urinary tract infection (UTI) 11 patients (4%) had a wound infection, and 30 patients (12%) had pneumonia. We diagnosed 35 cases of bacteremia (35%), whereas cytomegalovirus (CMV) infection was demonstrated in 40 patients (16%). Conclusions. Immunosuppressive therapy, necessary to avoid acute and chronic rejection, exposes patients to a higher rate of infectious complications. The immunosuppressive protocols led to a relatively low incidence of infectious complications, mainly of little clinical significance. The highest incidence was evident by the sixth month after transplantation, when the immunosuppressive regimen exercised its most depressive effects on patient immune systems.
From the Department of Surgery (M.V., G.G., D.C., M.G., D.V., T.T., D.Z., C.V., D.C., P.V.), Transplantation and Advanced Technologies – Organ Transplant Unit, and Department of Molecular Biology (V.S., A.S., S.S.), University Hospital of Catania, Catania, Italy.
Address reprint requests to Massimiliano Veroux, MD, PhD, Department of Surgical Sciences, Transplantation and Advanced Technologies – Organ Transplant Unit, University Hospital, Via S. Sofia, 78-95123 Catania, Italy. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.065
Transplantation Proceedings, 40, 1873–1876 (2008)
1873
1874
VEROUX, GIUFFRIDA, CORONA ET AL
K
IDNEY transplantation is the best available replacement therapy for patients with end-stage renal disease (ESRD). Although short-term results have recently improved, long-term results are not satisfactory probably as a consequence of the complications related to the immunosuppression. Infection is a common cause of morbidity and mortality among patients receiving chronic maintenance immunosuppression.1,2 It is the second cause of death after cardiovascular disease. The risk of infection following renal transplantation strictly depends on the recipient’s net state of immunosuppression, epidemiologic exposures, and consequences of the invasive procedures. Although infection-related mortality in the first year posttransplantation has been reduced to less than 5%, these complications remain serious threats for successful outcomes following kidney transplantation. The correct balance between the newer antirejection agents, such as mycophenolate mofetil (MMF) and sirolimus (SIR), and the use of antimicrobial, antiviral, and antifungal prophylactic regimens has become an integral part of medical therapy early after kidney transplantations.3 It has significantly reduced the incidence of early opportunistic infections. Herein we have presented a retrospective study evaluating the incidence and outcome of infections in a population of 245 renal transplant recipients.
complete blood cell count, serum electrolytes and creatinine, liver function tests, urinalysis, microbiological studies, viral antigen search, and immunosuppressive drug levels. Urinary tract infections (UTIs) were revealed clinically by fever, urgency, frequency, dysuria, and suprapubic tenderness or were diagnosed using isolation of an infectious agent upon culture. Asymptomatic cases were diagnosed only using a positive urine culture (ⱖ105 microrganisms/mm3).
PATIENTS AND METHODS
Surgical Wound Infection
This retrospective, observational study of 245 renal allograft recipients who underwent transplantation between January 2002 and December 2005 included 190 grafts procured from cadaveric donors and 55 from a living donor. One-hundred sixty recipients were females and 85 males of median age of 45.2 years (range, 24 – 67 years). All patients experienced a standardized posttransplantation immunosuppressive protocol: 102 patients were induced with basiliximab; the other 143 patients did not receive any induction therapy. One- hundred eighty patients received prednisolone, tacrolimus, and MMF; 65 patients received prednisolone, cyclosporine, and MMF. In the immunosuppressive protocol, prednisolone given at a dose of 1 mg/kg/d was slowly tapered to a maintenance dose of 5 mg/d by the end of the sixth month. MMF was given at a dose of 1 to 2 g/d. For patients receiving tacrolimus-based immunosuppression, tacrolimus was initiated at 0.1 mg/kg/d with doses adjusted to maintain levels between 10 and 12 ng/mL in the first month posttransplantation and then between 8 and 10 ng/mL. For recipients receiving cyclosporine-based immunosuppression, cyclosporine was started at 2 days after operation at 5 mg/kg/d with doses adjusted to keep trough levels at 200 –220 ng/mL for the first 3 months after the transplantation, then at 150 to 200 ng/mL between 3 and 6 months after the transplantation, and more than 140 ng/mL thereafter. In all seronegative recipients receiving a kidney from a cytomegalovirus (CMV)–seropositive donor (D⫹R⫺), we prescribed a 21-day course of intravenous prophylaxis with gancyclovir (2 mg/ kg/bid), and 900 mg/d oral valgancyclovir for 6 months. To detect any infectious process, patient conditions were followed by physical examination and laboratory studies, including
Eleven patients (4%) had a wound infection within 30 days from surgery. The isolated micro- organisms were P aeruginosa and Staphylococcus aureus in 8 patients and Streptococcus agalactiae in 2 patients, whereas a concomitant infection with C albicans was demonstrated in 1 patient.
RESULTS
A total of 110 (44.9%) patients developed an infectious process during the posttransplantation period for a total of 232 infective processes. UTI
During the first 6 months posttransplantation 80 patients (32 females, 28 males) developed at least 1 episode of UTI, representing the most frequent bacterial infection (71%). The most frequently isolated pathogens were Escherichia coli (47%) and Enterococcus fecalis (35.5%). Other pathogens were represented by Klebsiella pneumoniae (10.5%) and Pseudomonas aeruginosa (4.25%). Twenty patients (8.1%) developed a UTI by Candida albicans. Forty-nine episodes of UTI occurred in the first month posttransplantation, whereas 31 occurred within 6 months posttransplantation.
Pneumonia
Pneumonia was present in 30 patients (12%); the majority of cases occurred early posttransplantation. A specific diagnosis was established in only 25% Staphylococcus hemolyticus was isolated in the sputum of 5 patients. Seven patients developed Pneumocystis carinii pneumonia of whom 2 patients eventually died (mortality rate 28.5%). Four patients (1.6%) showed clinical and laboratory findings of invasive pulmonary aspergillosis, 1 of whom also showed an ocular localization of the infection. This patient lost her graft because of discontinuation of immunosuppression. All patients are alive with no clinical recurrence of aspergillosis. Bacteremia
There were 35 cases of bacteremia (35%). In most cases the source of the infection was the central venous catheter. Most of the pathogens isolated in 1 or more blood cultures were the same as those grown from the central venous catheter tip: E coli, E fecalis, S hemolyticus, and S aureus.
INFECTIVE COMPLICATIONS
CMV Infection
Clinically relevant CMV infection was demonstrated in 40 patients (16%). In 18 cases it was a primary infection, whereas 22 were endogenous reactivations. One patient died because of acute CMV-related hepatitis. Fungal Infections
Twenty-two patients presented with esophageal candidiasis, whereas 7 patients had urogenital candidiasis. Dysphagia was the most common presenting symptom of esophageal disease (83%), whereas recurrent UTIs were the leading symptom of urogenital candidiasis (95%). One patient lost her graft because of concomitant pulmonary aspergillosis, whereas 2 patients lost their grafts because of discontinuation of immunosuppression. DISCUSSION
Renal transplantation has become a well-established, highly successful therapy for chronic ESRD. Renal graft recipients are at greatest risk of infections that may compromise the transplant outcome and may represent a serious danger to the patient’s life. Infectious complications after renal transplantation are associated with significant morbidity. They are still the most frequent cause of death in the early posttransplantation period.2,4 – 6 Under standard immunosuppression, nearly 80% of all renal transplant recipients suffer at least 1 episode of infection during the first year after transplantation.7,8 Our study confirmed this trend, with more than 60% of patients developing at least 1 infectious process in the first year posttransplantation. About 50% of kidney transplant recipients develop bacterial infections. UTI is the most common type of bacterial infection among kidney transplant recipients with reported incidences ranging from 35% to 79%.9,10 Most infections develop in the early period posttransplantation with a high incidence of recurrence. The principal causative microorganisms are E coli and E fecalis.11 We observed a higher incidence of infections in the first 3 months after transplantation in contrast with the recent report by Alangaden et al,1 who noted a decreased incidence of UTI in the early period, probably as a result of a new antimicrobial prophylaxis regimen. Our higher incidence may be a result of stronger immunosuppression, and the presence of a double-J ureteral stent, which in our institution is usually removed within 3 months after transplantation. Fungal urinary infections are rare. In a recent study12 candiduria was noted in 11% of patients, with no differences in outcomes between the patients treated for asymptomatic candiduria and those who were not. We have previously reported13 a 5% incidence of invasive UTIs. Most of these infections are relatively benign, but they frequently recur, if untreated, they may cause graft loss. Invasive fungal infection, such as esophageal candidiasis, is relatively rare in kidney transplant recipients,
1875
with an incidence varying between 10% and 25%.13–15 The treatment may be challenging and, in such cases, the use of newer antifungal drugs, such as voriconazole or caspofungin, may be necessary to achieve a favorable outcome.13 Several studies have reported that the incidence of pulmonary infections ranges from 4.5% to 16%.5,16,17 We reported 30 cases (12%) of pneumonia, the majority of which occurred in the early period posttransplantation. Bacterial pulmonary infections are frequent and usually easily treated with antibiotic regimens. Pulmonary aspergillosis may be extremely aggressive; if not correctly treated it is fatal in the vast majority of patients. The use of voriconazole, in some cases in combination with caspofungin, may significantly reduce the mortality rate in these patients.18 The low number of SWI reported in recent reports19 is likely the result of improvement in surgical technique, good management of the surgical wound site, and adoption of a prophylactic antibiotic regimen. The incidence of SWI may be increased in diabetic patients and in patients treated with SIR. As confirmed by this retrospective study, the mortality rate due to infectious disease was relatively low among kidney transplant recipients, although it represents the second cause of death after cardiovascular complications.20 Although bacterial infection–related mortality remained stable, viral infection–related mortality decreased (31% vs 7%) and fungal infection-related mortality increased (11% vs 36%).20,21 Our data confirmed the observation that most infectious disease in kidney transplantation evolves in a favorable way. The highest incidence was evident by the sixth month after transplantation, when the effects of the immunosuppressive regimen most depressed the patient’s immune system and after their immunosuppression may have been increased due to episodes of rejection. The frequent occurrence of UTIs may probably be related to the physical status pretransplantation of most patients and to the presence of the double-J catheter, which mitigates urological complications, but increases the risk of UTIs. The low mortality rate was related to the better management of immunosuppressive therapy and the development of newer, efficacious antibiotics. However, the occurrence of life-threatening infections such as fungal or CMV diseases, requires rigorous management of immunosuppressive therapy to avoid lethal consequences. REFERENCES 1. Alangaden GJ, Thyagarajan R, Gruber SA, et al: Infectious complications after kidney transplantation: current epidemiology and associated risk factors. Clin Transplant 20:401, 2006 2. Pourmand G, Salem S, Mehrsai A, et al: Infectious complications after kidney transplantation: a single-center experience. Transpl Infect Dis 9:302, 2007 3. Chan L, Gaston R, Hariharan S: Evolution of immunosuppression and continued importance of acute rejection in renal transplantation. Am J Kidney Dis 38(suppl 6):S2, 2001
1876 4. Patel R, Paya CV: Infections in solid-organ transplant recipients. Clin Microbiol Rev 10:86, 1997 5. Fishman JA, Rubin RH: Infection in organ-transplant recipients. N Engl J Med 338:1741, 1998 6. Splendiani G, Cipriani S, Tisone G, et al: Infectious complications in renal transplant recipients. Transplant Proc 37:2497, 2005 7. Rubin RH: Infectious disease complications of renal transplantation. Kidney Int 44:221, 1993 8. Kumar MS, Cridge P, Molavi A, et al: Infectious complications in the first 100 days after renal transplantation. Transplant Proc 27:2705, 1995 9. Oguz Y, Bulucu F, Oktenli C, et al: Infectious complications in 135 Turkish renal transplant patients. Cent Eur J Public Health 10:153, 2002 10. Maraha B, Bonten H, van Hooff H, et al: Infectious complications and antibiotic use in renal transplant recipients during a 1-year follow-up. Clin Microbiol Infect 7:619, 2001 11. Valera B, Genti MA, Cabello V, et al: Epidemiology of urinary infections in rebal transplant recipients. Transplant Proc 38:2414, 2006 12. Safdar N, Slattery WR, Knasinski V, et al: Predictors and outcomes of candiduria in renal transplant recipients. Clin Infect Dis 15:1413, 2005 13. Veroux M, Macarone M, Fiamingo P, et al: Caspofungin in the treatment of azole-refractory esophageal candidiasis in kidney transplant recipients. Transplant Proc 38:1037, 2006
VEROUX, GIUFFRIDA, CORONA ET AL 14. Abbott KC, Hypolite I, Poropatich RK, et al: Hospitalizations for fungal infections after renal transplantation in the United States. Transpl Infect Dis 3:203, 2001 15. Gupta KL, Ghosh AK, Kochhar R, et al: Esophageal candidiasis after renal transplantation: comparative study in patients under different immunosuppressive protocols. Am J Gastroenterol 89:1062, 1994 16. Charfeddine K, Zaghden S, Kharrat M, et al: Infectious complications in kidney transplant recipients: a single-center experience. Transplant Proc 37:2823, 2005 17. Camargo LFA, Gomes PS, Machado PGP, et al: Management of pulmonary infections in kidney transplant patients. Clin Pulm Med 10:308, 2003 18. Veroux M, Corona D, Gagliano M, et al: Voriconazole in the treatment of invasive aspergillosis in kidney transplant recipients. Transplant Proc 39:1838, 2007 19. Humar A, Ramcharan T, Denny R, et al: Are wound complications in kidney transplant more common with modern immunosuppression? Transplantation 72:1920, 2001 20. Linares L, Cofàn F, Cervera C, et al: Infection-related mortality in a large cohort of renal transplant recipients. Transplant Proc 39:2225, 2007 21. Dharnidharka VR, Agodoa LY, Abbott KC: Risk factors for hospitalization for bacterial or viral infection in renal transplant recipients - An analysis of USRDS data. Am J Transplant 7:653, 2007
Infective Complications in Renal Allograft Recipients: Epidemiology and Outcome M. Veroux, G. Giuffrida, D. Corona, M. Gagliano, V. Scriffignano, D. Vizcarra, T. Tallarita, D. Zerbo, C. Virgilio, A. Sciacca, D. Cappello, S. Stefani, and P. Veroux ABSTRACT Introduction. Successful renal transplantation strictly depends on good control of rejection and better prevention and treatment of infections, which remain serious threats. Methods. This retrospective, observational study of 245 renal allograft recipients who underwent transplantation between January 2002 and December 2005 included a 21 ⫾ 10 months follow-up. Results. A total of 110 (44.9%) patients developed an infective process during the posttransplantation period, namely, 232 infective processes. Eighty patients developed at least 1 episode of urinary tract infection (UTI) 11 patients (4%) had a wound infection, and 30 patients (12%) had pneumonia. We diagnosed 35 cases of bacteremia (35%), whereas cytomegalovirus (CMV) infection was demonstrated in 40 patients (16%). Conclusions. Immunosuppressive therapy, necessary to avoid acute and chronic rejection, exposes patients to a higher rate of infectious complications. The immunosuppressive protocols led to a relatively low incidence of infectious complications, mainly of little clinical significance. The highest incidence was evident by the sixth month after transplantation, when the immunosuppressive regimen exercised its most depressive effects on patient immune systems.
From the Department of Surgery (M.V., G.G., D.C., M.G., D.V., T.T., D.Z., C.V., D.C., P.V.), Transplantation and Advanced Technologies – Organ Transplant Unit, and Department of Molecular Biology (V.S., A.S., S.S.), University Hospital of Catania, Catania, Italy.
Address reprint requests to Massimiliano Veroux, MD, PhD, Department of Surgical Sciences, Transplantation and Advanced Technologies – Organ Transplant Unit, University Hospital, Via S. Sofia, 78-95123 Catania, Italy. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.065
Transplantation Proceedings, 40, 1873–1876 (2008)
1873
1874
VEROUX, GIUFFRIDA, CORONA ET AL
K
IDNEY transplantation is the best available replacement therapy for patients with end-stage renal disease (ESRD). Although short-term results have recently improved, long-term results are not satisfactory probably as a consequence of the complications related to the immunosuppression. Infection is a common cause of morbidity and mortality among patients receiving chronic maintenance immunosuppression.1,2 It is the second cause of death after cardiovascular disease. The risk of infection following renal transplantation strictly depends on the recipient’s net state of immunosuppression, epidemiologic exposures, and consequences of the invasive procedures. Although infection-related mortality in the first year posttransplantation has been reduced to less than 5%, these complications remain serious threats for successful outcomes following kidney transplantation. The correct balance between the newer antirejection agents, such as mycophenolate mofetil (MMF) and sirolimus (SIR), and the use of antimicrobial, antiviral, and antifungal prophylactic regimens has become an integral part of medical therapy early after kidney transplantations.3 It has significantly reduced the incidence of early opportunistic infections. Herein we have presented a retrospective study evaluating the incidence and outcome of infections in a population of 245 renal transplant recipients.
complete blood cell count, serum electrolytes and creatinine, liver function tests, urinalysis, microbiological studies, viral antigen search, and immunosuppressive drug levels. Urinary tract infections (UTIs) were revealed clinically by fever, urgency, frequency, dysuria, and suprapubic tenderness or were diagnosed using isolation of an infectious agent upon culture. Asymptomatic cases were diagnosed only using a positive urine culture (ⱖ105 microrganisms/mm3).
PATIENTS AND METHODS
Surgical Wound Infection
This retrospective, observational study of 245 renal allograft recipients who underwent transplantation between January 2002 and December 2005 included 190 grafts procured from cadaveric donors and 55 from a living donor. One-hundred sixty recipients were females and 85 males of median age of 45.2 years (range, 24 – 67 years). All patients experienced a standardized posttransplantation immunosuppressive protocol: 102 patients were induced with basiliximab; the other 143 patients did not receive any induction therapy. One- hundred eighty patients received prednisolone, tacrolimus, and MMF; 65 patients received prednisolone, cyclosporine, and MMF. In the immunosuppressive protocol, prednisolone given at a dose of 1 mg/kg/d was slowly tapered to a maintenance dose of 5 mg/d by the end of the sixth month. MMF was given at a dose of 1 to 2 g/d. For patients receiving tacrolimus-based immunosuppression, tacrolimus was initiated at 0.1 mg/kg/d with doses adjusted to maintain levels between 10 and 12 ng/mL in the first month posttransplantation and then between 8 and 10 ng/mL. For recipients receiving cyclosporine-based immunosuppression, cyclosporine was started at 2 days after operation at 5 mg/kg/d with doses adjusted to keep trough levels at 200 –220 ng/mL for the first 3 months after the transplantation, then at 150 to 200 ng/mL between 3 and 6 months after the transplantation, and more than 140 ng/mL thereafter. In all seronegative recipients receiving a kidney from a cytomegalovirus (CMV)–seropositive donor (D⫹R⫺), we prescribed a 21-day course of intravenous prophylaxis with gancyclovir (2 mg/ kg/bid), and 900 mg/d oral valgancyclovir for 6 months. To detect any infectious process, patient conditions were followed by physical examination and laboratory studies, including
Eleven patients (4%) had a wound infection within 30 days from surgery. The isolated micro- organisms were P aeruginosa and Staphylococcus aureus in 8 patients and Streptococcus agalactiae in 2 patients, whereas a concomitant infection with C albicans was demonstrated in 1 patient.
RESULTS
A total of 110 (44.9%) patients developed an infectious process during the posttransplantation period for a total of 232 infective processes. UTI
During the first 6 months posttransplantation 80 patients (32 females, 28 males) developed at least 1 episode of UTI, representing the most frequent bacterial infection (71%). The most frequently isolated pathogens were Escherichia coli (47%) and Enterococcus fecalis (35.5%). Other pathogens were represented by Klebsiella pneumoniae (10.5%) and Pseudomonas aeruginosa (4.25%). Twenty patients (8.1%) developed a UTI by Candida albicans. Forty-nine episodes of UTI occurred in the first month posttransplantation, whereas 31 occurred within 6 months posttransplantation.
Pneumonia
Pneumonia was present in 30 patients (12%); the majority of cases occurred early posttransplantation. A specific diagnosis was established in only 25% Staphylococcus hemolyticus was isolated in the sputum of 5 patients. Seven patients developed Pneumocystis carinii pneumonia of whom 2 patients eventually died (mortality rate 28.5%). Four patients (1.6%) showed clinical and laboratory findings of invasive pulmonary aspergillosis, 1 of whom also showed an ocular localization of the infection. This patient lost her graft because of discontinuation of immunosuppression. All patients are alive with no clinical recurrence of aspergillosis. Bacteremia
There were 35 cases of bacteremia (35%). In most cases the source of the infection was the central venous catheter. Most of the pathogens isolated in 1 or more blood cultures were the same as those grown from the central venous catheter tip: E coli, E fecalis, S hemolyticus, and S aureus.
INFECTIVE COMPLICATIONS
CMV Infection
Clinically relevant CMV infection was demonstrated in 40 patients (16%). In 18 cases it was a primary infection, whereas 22 were endogenous reactivations. One patient died because of acute CMV-related hepatitis. Fungal Infections
Twenty-two patients presented with esophageal candidiasis, whereas 7 patients had urogenital candidiasis. Dysphagia was the most common presenting symptom of esophageal disease (83%), whereas recurrent UTIs were the leading symptom of urogenital candidiasis (95%). One patient lost her graft because of concomitant pulmonary aspergillosis, whereas 2 patients lost their grafts because of discontinuation of immunosuppression. DISCUSSION
Renal transplantation has become a well-established, highly successful therapy for chronic ESRD. Renal graft recipients are at greatest risk of infections that may compromise the transplant outcome and may represent a serious danger to the patient’s life. Infectious complications after renal transplantation are associated with significant morbidity. They are still the most frequent cause of death in the early posttransplantation period.2,4 – 6 Under standard immunosuppression, nearly 80% of all renal transplant recipients suffer at least 1 episode of infection during the first year after transplantation.7,8 Our study confirmed this trend, with more than 60% of patients developing at least 1 infectious process in the first year posttransplantation. About 50% of kidney transplant recipients develop bacterial infections. UTI is the most common type of bacterial infection among kidney transplant recipients with reported incidences ranging from 35% to 79%.9,10 Most infections develop in the early period posttransplantation with a high incidence of recurrence. The principal causative microorganisms are E coli and E fecalis.11 We observed a higher incidence of infections in the first 3 months after transplantation in contrast with the recent report by Alangaden et al,1 who noted a decreased incidence of UTI in the early period, probably as a result of a new antimicrobial prophylaxis regimen. Our higher incidence may be a result of stronger immunosuppression, and the presence of a double-J ureteral stent, which in our institution is usually removed within 3 months after transplantation. Fungal urinary infections are rare. In a recent study12 candiduria was noted in 11% of patients, with no differences in outcomes between the patients treated for asymptomatic candiduria and those who were not. We have previously reported13 a 5% incidence of invasive UTIs. Most of these infections are relatively benign, but they frequently recur, if untreated, they may cause graft loss. Invasive fungal infection, such as esophageal candidiasis, is relatively rare in kidney transplant recipients,
1875
with an incidence varying between 10% and 25%.13–15 The treatment may be challenging and, in such cases, the use of newer antifungal drugs, such as voriconazole or caspofungin, may be necessary to achieve a favorable outcome.13 Several studies have reported that the incidence of pulmonary infections ranges from 4.5% to 16%.5,16,17 We reported 30 cases (12%) of pneumonia, the majority of which occurred in the early period posttransplantation. Bacterial pulmonary infections are frequent and usually easily treated with antibiotic regimens. Pulmonary aspergillosis may be extremely aggressive; if not correctly treated it is fatal in the vast majority of patients. The use of voriconazole, in some cases in combination with caspofungin, may significantly reduce the mortality rate in these patients.18 The low number of SWI reported in recent reports19 is likely the result of improvement in surgical technique, good management of the surgical wound site, and adoption of a prophylactic antibiotic regimen. The incidence of SWI may be increased in diabetic patients and in patients treated with SIR. As confirmed by this retrospective study, the mortality rate due to infectious disease was relatively low among kidney transplant recipients, although it represents the second cause of death after cardiovascular complications.20 Although bacterial infection–related mortality remained stable, viral infection–related mortality decreased (31% vs 7%) and fungal infection-related mortality increased (11% vs 36%).20,21 Our data confirmed the observation that most infectious disease in kidney transplantation evolves in a favorable way. The highest incidence was evident by the sixth month after transplantation, when the effects of the immunosuppressive regimen most depressed the patient’s immune system and after their immunosuppression may have been increased due to episodes of rejection. The frequent occurrence of UTIs may probably be related to the physical status pretransplantation of most patients and to the presence of the double-J catheter, which mitigates urological complications, but increases the risk of UTIs. The low mortality rate was related to the better management of immunosuppressive therapy and the development of newer, efficacious antibiotics. However, the occurrence of life-threatening infections such as fungal or CMV diseases, requires rigorous management of immunosuppressive therapy to avoid lethal consequences. REFERENCES 1. Alangaden GJ, Thyagarajan R, Gruber SA, et al: Infectious complications after kidney transplantation: current epidemiology and associated risk factors. Clin Transplant 20:401, 2006 2. Pourmand G, Salem S, Mehrsai A, et al: Infectious complications after kidney transplantation: a single-center experience. Transpl Infect Dis 9:302, 2007 3. Chan L, Gaston R, Hariharan S: Evolution of immunosuppression and continued importance of acute rejection in renal transplantation. Am J Kidney Dis 38(suppl 6):S2, 2001
1876 4. Patel R, Paya CV: Infections in solid-organ transplant recipients. Clin Microbiol Rev 10:86, 1997 5. Fishman JA, Rubin RH: Infection in organ-transplant recipients. N Engl J Med 338:1741, 1998 6. Splendiani G, Cipriani S, Tisone G, et al: Infectious complications in renal transplant recipients. Transplant Proc 37:2497, 2005 7. Rubin RH: Infectious disease complications of renal transplantation. Kidney Int 44:221, 1993 8. Kumar MS, Cridge P, Molavi A, et al: Infectious complications in the first 100 days after renal transplantation. Transplant Proc 27:2705, 1995 9. Oguz Y, Bulucu F, Oktenli C, et al: Infectious complications in 135 Turkish renal transplant patients. Cent Eur J Public Health 10:153, 2002 10. Maraha B, Bonten H, van Hooff H, et al: Infectious complications and antibiotic use in renal transplant recipients during a 1-year follow-up. Clin Microbiol Infect 7:619, 2001 11. Valera B, Genti MA, Cabello V, et al: Epidemiology of urinary infections in rebal transplant recipients. Transplant Proc 38:2414, 2006 12. Safdar N, Slattery WR, Knasinski V, et al: Predictors and outcomes of candiduria in renal transplant recipients. Clin Infect Dis 15:1413, 2005 13. Veroux M, Macarone M, Fiamingo P, et al: Caspofungin in the treatment of azole-refractory esophageal candidiasis in kidney transplant recipients. Transplant Proc 38:1037, 2006
VEROUX, GIUFFRIDA, CORONA ET AL 14. Abbott KC, Hypolite I, Poropatich RK, et al: Hospitalizations for fungal infections after renal transplantation in the United States. Transpl Infect Dis 3:203, 2001 15. Gupta KL, Ghosh AK, Kochhar R, et al: Esophageal candidiasis after renal transplantation: comparative study in patients under different immunosuppressive protocols. Am J Gastroenterol 89:1062, 1994 16. Charfeddine K, Zaghden S, Kharrat M, et al: Infectious complications in kidney transplant recipients: a single-center experience. Transplant Proc 37:2823, 2005 17. Camargo LFA, Gomes PS, Machado PGP, et al: Management of pulmonary infections in kidney transplant patients. Clin Pulm Med 10:308, 2003 18. Veroux M, Corona D, Gagliano M, et al: Voriconazole in the treatment of invasive aspergillosis in kidney transplant recipients. Transplant Proc 39:1838, 2007 19. Humar A, Ramcharan T, Denny R, et al: Are wound complications in kidney transplant more common with modern immunosuppression? Transplantation 72:1920, 2001 20. Linares L, Cofàn F, Cervera C, et al: Infection-related mortality in a large cohort of renal transplant recipients. Transplant Proc 39:2225, 2007 21. Dharnidharka VR, Agodoa LY, Abbott KC: Risk factors for hospitalization for bacterial or viral infection in renal transplant recipients - An analysis of USRDS data. Am J Transplant 7:653, 2007